Project Summary/Abstract: Many pathogenic bacteria utilize protein-based nanoreactors called bacterial microcompartments to metabolize diverse nutritional sources. This helps pathogenic organisms thrive in human tissues. The bacterial microcompartment is a specialized organelle composed of enzymes surrounded by a protein shell. To function, compounds to be broken down within the bacterial microcompartment must cross the shell and, likewise, the breakdown products must egress the compartments. The goal of the proposed research is to study and disrupt the protein-protein interactions essential for shell integrity. In parallel, we will characterize the permeability properties of BMC shells, and screen for compounds that interfere with flux across the shells. Collectively these data will provide new knowledge about the structural basis of shell function and provide the foundation for producing therapeutics that disrupt shell assembly and permeability.